L0301P27 - Chromosome Disorders
Chromosome *DNA intercalated around histones to form nucleosomes which coils into chromatin *chromatin compacts into chromosomes during cell division *two chromatids joined at the centrosome Chromosome Arms *p (petite) = short arm *q = long arm *separated by the centromere Morphological Classification *constant for a particular chromosome *3 subgroups according to the position of the centromere: **metacentric (left) ***centromere near the middle ***p ≃ q **submetacentric (middle) ***centromere between the middle and end of the chromosome ***p < q **acrocentric (right) ***centromere on the end ***p basically 0 Karyotype *number and appearance of chromosomes in an individual *humans: **46 chromosomes in somatic cells **23 chromosomes in gametes **22 pairs of autosomal chromosomes **1 pair of sex chromosomes Describing Karyotypes #total number of chromosomes #sex chromosome makeup #description of any observed abnormality *e.g.: **46,XY - normal male **46,XX - normal female **47,XX,+21 - female Down syndrome **46,XX,del(5p) - female with a deletion of the shorn arm of chromosome 5 Chromosome Analysis *tissue with living nucleated cells that undergo division *often: lymphocytes from peripheral blood *other sources: amniotic fluid, chorionic villi, bone marrow Colchicine *added to cells to stop them from dividing at the metaphase stage so they can be analysed Giemsa Staining and G-Banding *stain used on chromosomes showing G-bands which are: **alternating light and dark bands **light bands contain most active genes **banding pattern is characteristic of each chromosome pair **banding allows precise identification of each chromosome **deletions or insertions of >4Mb of DNA can be identified   Karyotype Analysis *counting chromosomes: metaphase spreads *analysis of banding pattern of each chromosome *shown as a stylised karyotype or ideogram Ideogram *a stylised karyotype *a standardised numbering system used for bands seen in G-banding *allows detection of abnormalities *used for determining location of genes on chromosome Chromosomal Abnormalities *account for most spontaneous pregnancy loss and childhood disability *10% abnormality form sperm, 25% abnormality from egg *may involve changes in autosomes or sex chromosomes **numerical **structural Numerical ---- Aneuploidy *loss or gain of one or more chromosomes *results from non-disjunction at anaphase during first or second meiotic divisions *OR after fertilisation in the early stages during mitosis - mosaicism - not all cells are affected (monosomy cell is not viable) Monosomy *loss of a single chromosome *usually lethal before term *foetus sometimes lives if it is the sex chromosome that is missing **e.g. Turner syndrome - 45, X Trisomy *extra chromosome **generally autosome *examples **Edwards - tri18 ***95% abort spontaneously **Patau - tri13 ***usually maternal nondisjunction ***dysmorphic features at birth **Down - tri21 ***>60% abort spontaneously ***usually maternal origin - 95% Polyploidy *multiple of haploid number >2n *lethal *e.g. 69,XXX - triploidy *caused by: **fertilisation by two sperm **fertilisation by a diploid sperm **fertilisation of a diploid egg (not viable) *however occurs normally in bone marrow cells: megakaryocytes to produce platelets **generally 8-16n Structural ---- Chromosome Abnormalities Balanced Rearrangement *no net loss of gain *usually harmless unless breakpoint interrupts an important functional gene *carriers have higher risk of producing offspring with unbalanced chromosome complement Unbalanced Rearrangement *net loss or gain *clinical effects are usually severe Translocations Robertsonian *short arms of two acrocentric chromosomes are lost *long arms fuse at centromere to make a single chromosome *may lead to tri21 Reciprocal *portion of two chromosomes break and exchange *when DNA is similar and incorrectly recognised as homologous Insertional and Deletional *portion of one chromosome gets inserted into another Inversion *portion of DNA gets inverted